BRC/ABL transgenic animals as models for Philadelphia chromosome positive chronic myelogenous and acute lymphoblastic leukemia

Abstract

The present invention relates to non-human transgenic animals which contain a transgene comprising a BCR/ABL gene fusion and which develop leukemia. In a preferred embodiment of the present invention, the transgenic animals exhibit a rapid induction of acute leukemia. The present invention offers the advantage of providing, for the first time, a non-human transgenic animal model system which carries the BCR/ABL gene fusion characteristic of the Philadelphia chromosome and which develops leukemia in a manner directly analogous to the clinical progression of chronic myelogenous leukemia (CML) and/or acute lymphoblastic leukemia (ALL) in humans. This model system for human leukemia may be valuable in obtaining a better understanding of CML and ALL and in developing effective therapeutic regimens.

What is claimed is: 
     
       1. A transgenic mouse which carries a BCR/C-ABL transgene that comprises at least the first exon of a BCR gene and a functional portion of a c-ABL gene under the control of a metallothionine promoter sequence in its somatic and germ cells, whereby said BCR/c-ABL transgene is expressed in its bone marrow cells and is effective for promoting a leukemia in said mouse. 
     
     
       2. The transgenic mouse of claim 1 in which the BCR/c-ABL transgene comprises non-human c-ABL sequence. 
     
     
       3. The transgenic mouse of claim 1 in which the BCR/c-ABL transgene comprises human c-ABL sequence. 
     
     
       4. The transgenic mouse of claim 1 in which the BRC/c-ABL transgene further comprises a portion of the third exon of the c-ABL gene. 
     
     
       5. The transgenic mouse of claim 1 in which the BCR/c-ABL transgene further comprises the second exon of the c-ABL gene. 
     
     
       6. The transgenic mouse of claim 2 in which the BCR/c-ABL transgene further comprises an exon of the Mbcr region of the BCR gene. 
     
     
       7. The transgenic mouse of claim 3 in which the BCR/c-ABL transgene further comprises an exon of the Mbcr region of the BCR gene. 
     
     
       8. The transgenic mouse of claim 1, 2, or 3 in which the BCR/c-ABL transgene further comprises exons two through eleven of the c-ABL gene. 
     
     
       9. The transgenic mouse of claim 1, 2, in or 3, in which the BCR/c-ABL transgene further comprises an exon of the Mbcr region of the BCR gene and exons two through eleven of the c-ABL gene. 
     
     
       10. The Mouse of claim 6 or 7 in which the BCR/c-ABL transgene is effective for promoting a chronic myelocytic leukemia in said mouse. 
     
     
       11. The mouse of claim 1 in which the BCR/c-ABL transgene is effective for promoting an acute lymphoblastic leukemia in said mouse 
     
     
       12. The mouse of claim 1, wherein said mouse is produced using embryonic stem cells into which the BCR/c-ABL transgene has been introduced. 
     
     
       13. The transgenic mouse of claim 10 wherein said BCR/c-ABL transgene comprises human c-ABL sequence. 
     
     
       14. The transgenic mouse of claim 11 wherein said BCR/c-ABL transgene comprises human c-ABL sequence. 
     
     
       15. The transgenic mouse of claim 12 wherein said BCR/c-ABL transgene comprises human c-ABL sequence.